RESUMO
It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N-acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid reliably reduce ischemia-induced depression of inotropic functions of the left ventricle in cats with experimental myocardial infarction model. The effect of both compounds can be explained by the maintenance of viability of the injured myocardium via a delay of the development of acidosis and the support of oxygen recycling in the ischemized zone. Both compounds show pronounced antiradical properties with a non-standard mechanism of action.
Assuntos
Acetatos/farmacologia , Hidrazinas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Ácidos Fosfóricos/farmacologia , Acetatos/uso terapêutico , Animais , Gatos , Modelos Animais de Doenças , Hidrazinas/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/fisiopatologia , Consumo de Oxigênio , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
In vivo and in vitro experiments revealed the neuroprotective activity of CAPAH, a representative of the new nootropic class phosphorylated carboxylic acid hydrazides. The mechanisms of this action, which were due to the membranous stabilizing activity of the drug and its affinity for glycine strychnine-sensitive sites of MMDA receptors (Ki = 8.8.10(-5) M). Six analogues of CAPAH have been also found to have affinity for these types of receptors; based on the examination of structure-affinity relationship, putative pharmacophores (only radicals of the benzene ring of a molecule in the para position exerted effects on affinity changes) were revealed. The findings give a deep insight into the mechanism of nootropic activity and open vistas for synthesizing phosphorylated carboxylic acid hydrazides as potential neuroprotective agents interacting with glycine strychnine-sensitive sites of MMDA receptor.
Assuntos
Acetatos/farmacologia , Isquemia Encefálica/prevenção & controle , Hidrazinas/farmacologia , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Acetatos/química , Marcadores de Afinidade/química , Marcadores de Afinidade/farmacologia , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Células Cultivadas , Hidrazinas/química , Camundongos , Neurônios/metabolismo , Nootrópicos/química , RatosAssuntos
Acetatos/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Hidrazinas/farmacologia , Nootrópicos/farmacologia , Animais , Espectroscopia de Ressonância de Spin Eletrônica , Membrana Eritrocítica/química , Hipóxia/sangue , Técnicas In Vitro , Lipídeos de Membrana/química , Membranas Artificiais , Osmose , Fosfatidilcolinas/química , Ratos , Espectrofotometria InfravermelhoRESUMO
Genotoxic action of four possible metabolites of the new tranquilizer phosphabenzide (acetylphosphabenzide, diphenylphosphinylacetic acid, phosphabenzide hydrazone with pyruvic acid, bis-1,2-(diphenylphosphinylacetyl)hydrazine) has been studied. These metabolites belong to slightly toxic phosphororganic compounds. The Ames Salmonella/microsomes tests performed on strains TA100 and TA98 showed that of these compounds only acetylphosphabenzide possessed mutagenic action. Metabolic activation of liver microsomes decreased the mutagenic effect. The mechanism of action of acetylphosphabenzide is likely to involve the formation of acetylhydrazine, capable of producing active electrophiles attacking DNA.
